The rapid development of the human brain, and its heightened sensitivity to environmental influences, in the first months of life determine critical brain-behavior relationships in childhood and across the lifespan. Despite evidence that the effects of poor caregiving on developing neurobiological systems underlying psychopathology risk may be most influential in the early years, little is known about the interface among neurobiological, affective and developmental areas of study in human infancy. In the proposed short-term prospective study, we wish to perform neuroimaging assessments in infancy (3 months), to provide a unique opportunity to identify prefrontal cortical-subcortical neural circuity structure and function associated with infant emotional reactivity at a critical stage in human neurodevelopment. In addition, we aim to examine the prospective relationships with infant emotional regulation capacity at 9 months, and the influence of maternal caregiving. We propose to identify 72 3-month-old infants of young, urban-living mothers at risk for compromised caregiving by virtue of their own negative parenting experiences, and dysregulated affect. The first aim of the proposed study is to identify neuroimaging measures of structure and intrinsic functional connectivity in emotional reactivity neural circuitry that are associated with negative and positive emotional reactivity in 3-month olds. We will examine the following three neuroimaging modalities in infants: 1) structural neuroimaging measures of prefrontal cortical and subcortical volumes and cortical thickness; 2) diffusion imaging measures of white matter structure in key tracts connecting prefrontal and subcortical, and prefrontal and other cortical, regions and 3) intrinsic (resting state) functional connectivity among these regions, and larger scale neural networks. The second aim is to determine prospective relationships between neural circuitry structure and intrinsic functional connectivity at 3 months and later emotional regulation at 9 months. The third aim is to determine the extent to which observed maternal caregiving behavior moderates the relationships in Aim 2. Exploratory analyses will examine the impact of infant gender upon brain-behavior relationships, and will also examine global neural connectivity in infants, and relationships with the above measures of infant emotional reactivity, 9-month emotional regulation, and maternal caregiving. By aiming to elucidate early neurobiological markers of infant emotional reactivity, relationships with subsequent emotional dysregulation, and the ways in which maternal caregiving impacts these brain-behavior relationships, the proposed research may ultimately provide neurobiological targets to guide early interventions to improve the health and well-being of at-risk children.